Why have the overhead of the browser at all?

Because everyone pretty much already has a browser installed on their desktop, and they're already familiar w/ navigating inside the browser. And, at least for Firefox (and maybe Opera), the browsers have already solved much of the platform/OS compatibility issues.

GUI tookits, OTOH, - and esp, in my experience, Perl GUI toolkits - tend to have mixed success addressing the platform independence requirement.

I think some of your assumptions wrt browser capabilities may be a bit dated; XUL brings much functionality to the Firefox browser, and when XAML becomes "official" in '06(?), it will likely further change user expectations wrt browser capabilities.

Hence, the need for "plugins" may go away, and by writing MVC structured apps - w/ very loose coupling between the M and the V -, GUI apps become small local web servers, at the same time providing the option for remote execution for apps that need it. Whether the user needs a Perl - or Java or Python or C# or etc. - installation on their desktop will depend entirely on the complexity of the app, and the speed of their 'net connection (tho the security issues remain problematic).

So, wrt the OP, it would be nice to have a decent Perl API in development now to address the likely future transition to browser based GUIs, even if the widget set were limited to XUL/Firefox for the time being.